Improved methods are needed that identify pulmonary endothelial injury in the lung prior to overwhelming loss of lung function. Such methods should lead to more precise definitions of the onset and course of these injuries, as well as the influence of potential therapeutic agents. This proposal describes experiments that evaluate and develop two methods to detect lung injury. By design they are sensitive and do not give false positive information from injuries to nonpumonary endothelial surfaces. Because Type II pneumocytes and surfactant contain proteins that are specific for the lung, antibodies to these proteins will be specific for lung tissue. Using monoclonal antibodies, an assay will be developed with sufficient sensitivity to detect surfactant proteins that leak through the injured lung endothelial surface into the blood and urine. This detection system for lung injury will be tested in animals subjected to air emboli, oleic acid emboli, and endotoxin injury. Because of the close proximity between alveolar endothelial and epithelial surfaces, endothelial injury will likely cause epithelial injury and increased permeability of both barriers. Then inhaled aerosols of lipophobic material deposited on the distal bronchiolar and alveolar surfaces should move more rapidly than usual into the blood. We will test this hypothesis by measuring the clearance of Technetium labelled diethylaminetriaminepentaacetate (99mTc-DTPA) aerosols from the lungs using gamma cameras, as well aas the rate of accumulation in the blood. Aerosol size, breathing patterns, and different compounds will be tested to develop a sensitive means of detecting altered endothelial permeability. Using the best methods developed in animals, both techniques will be evaluated in humans with endothelial injury from cardiopulmonary bypass, hemodialysis, and the acute respiratory distress syndrome.